Objective Increasing evidence indicates that intestinal microbiota play a role in diverse metabolic processes via intestinal butyrate production. Human bariatric surgery data suggest that the gut-brain axis is also involved in this process, but the underlying mechanisms remain unknown. Methods We compared the effect of fecal microbiota transfer (FMT) from post-Roux-en-Y gastric bypass (RYGB) donors vs oral butyrate supplementation on ( 123 I-FP-CIT-determined) brain dopamine transporter (DAT) and serotonin transporter (SERT) binding as well as stable isotope-determined insulin sensitivity at baseline and after 4 weeks in 24 male and female treatment-naïve metabolic syndrome subjects. Plasma metabolites and fecal microbiota were also determined at these time points. Results We observed an increase in brain DAT after donor FMT compared to oral butyrate that reduced this binding. However, no effect on body weight and insulin sensitivity was demonstrated after post-RYGB donor feces transfer in humans with metabolic syndrome. Increases in fecal levels of Bacteroides uniformis were significantly associated with an increase in DAT, whereas increases in Prevotella spp. showed an inverse association. Changes in the plasma metabolites glycine, betaine, methionine, and lysine (associated with the S -adenosylmethionine cycle) were also associated with altered striatal DAT expression. Conclusions Although more and larger studies are needed, our data suggest a potential gut microbiota-driven modulation of brain dopamine and serotonin transporters in human subjects with obese metabolic syndrome. These data also suggest the presence of a gut-brain axis in humans that can be modulated. NTR registration 4488.

Mammals perceive the five different taste qualities: bitter, sweet, umami, sour, and salty. At least two different mechanisms contribute to salt taste in rodents. One is elicited by various cations and sensitive to cetylpyridinium chloride, whereas another is selectively stimulated by Na + and inhibited by amiloride. The latter pathway has been suggested to involve the epithelial sodium channel, ENaC. In humans, the presence of amiloride-sensitive salt taste transduction is being disputed. In this paper, we addressed the question whether ENaC may have a role in human salt taste perception. Immunohistochemistry revealed that β-, γ-, and δ-ENaC subunits are present in subsets of circumvallate and fungiform taste bud cells, whereas α-ENaC was confined to cells of circumvallate taste buds. Alpha-, β-, and γ-subunits were observed in basolateral intracellular compartments, while δ-ENaC was exclusively found in all taste pores of both types of papillae consistent with a function in taste transduction. To further assess the involvement of ENaC in salt taste transduction, we combined sensory studies and functional expression of ENaC in oocytes. With the exception of L-homoarginine, choline chloride, L-arginine, L-lysine, and L-argininyl-Larginine enhanced both salt taste perception in subjects and sodium currents recorded in αβγ-or δβγ-ENaC expressing oocytes, whereas L-glutamine did neither show salttaste-enhancing activity nor did it influence the sodium currents in the oocyte assay. Taken together, our data make ENaC an interesting molecule possibly involved in salty taste transduction.

The typical bitter taste of beer is caused by adding hops (Humulus lupulus L.) during the wort boiling process. The bitter taste of hop-derived compounds was found to be mediated by three bitter taste receptors: TAS2R1, TAS2R14, and TAS2R40. In this work, structural bioinformatics analyses were used to characterize the binding modes of trans-isocohumulone, trans-isohumulone, trans-isoadhumulone, cis-isocohumulone, cis-isohumulone, cis-isoadhumulone, cohumulone, humulone, adhumulone, and 8-prenylnaringenin into the orthosteric binding site of their cognate receptors. A conserved asparagine in transmembrane 3 was found to be essential for the recognition of hop-derived compounds, whereas the surrounding residues in the binding site of the three receptors encode the ligand specificity. Hop-derived compounds are renowned bioactive molecules and are considered as potential hit molecules for drug discovery to treat metabolic diseases. A chemoinformatics analysis revealed that hop-derived compounds cluster in a different region of the chemical space compared to known bitter food-derived compounds, pinpointing hop-derived compounds as a very peculiar class of bitter compounds.

A rapid, high-throughput method for the quantitation of the 2-acetyl azaheterocycles, 2-acetyl-1-pyrroline, 2-acetyl-1,4,5,6-tetrahydropyridine, 2-acetylpyrazine, and 2-acetyl-2-thiazoline, in different food products, by liquid chromatography–tandem mass spectrometry (LC–MS/MS), was developed. The quick extraction by bead beater homogenization, fast derivatization by 3-nitrophenylhydrazine (40 °C, 2 h), and efficient LC separation make this method suitable for high-throughput analysis. As established in this study, the highly precise LC–MS/MS method applies to different food products or beverages without requiring further adjustment. The analysis was performed with sample amounts of 0.2–0.5 g, and limit of quantitation values of 0.6, 0.5, 0.6, and 1.0 μg/kg were obtained for 2-acetyl-1-pyrroline, 2-acetyl-1,4,5,6-tetrahydropyridine, 2-acetylpyrazine, and 2-acetyl-2-thiazoline, respectively. Thus, it was possible to quantitate the analytes in the range of their odor thresholds.

For the accurate quantitation of kokumi-enhancing and bitter-tasting octadecadien-12-ynoic and octadecadienoic acids in chanterelles (Cantharellus cibarius Fr.), a sensitive ultra-high-performance liquid chromatography−differential ion mobility spectrometry−tandem mass spectrometry method was developed. On the basis of these quantitative data and the taste thresholds, dose-over-threshold factors were calculated to determine the contribution of these sensometabolites to the kokumi and bitter taste of chanterelles; e.g., 14,15-dehydrocrepenynic acid (3) and (9Z,15E)-14-oxooctadeca-9,15-dien-12-ynoic acid (7) were identified as key kokumi substances in raw chanterelles. Quantitative profiling of these compounds in various mushroom species demonstrated a unique accumulation of octadecadien-12-ynoic acids in Cantharellus. Furthermore, storage experiments highlighted dynamic processes, including the biosynthesis of these substances as a result of lipid peroxidation mechanisms.